|US brand name: Depakote|
|Generic name: divalproex sodium|
side effects, dosage, how to take & discontinue, uses, pros & cons, and more
Table of Contents (hide)
- 1. Other brand names & branded generic names1
- 2. FDA Approved Uses of Depakote (divalproex sodium):
- 3. Depakote (divalproex sodium) Off-Label Uses
- 4. Depakote pros and cons
- 5. Depakote (divalproex sodium) Side Effects
- 6. Interesting Stuff Your Doctor Probably Won’t Tell You about Depakote (divalproex sodium)
- 7. Depakote Dosage and How to Take Depakote (divalproex sodium)
- 8. How Long Depakote Takes to Work
- 9. How to Stop Taking Depakote
- 10. Depakote Half-Life & Average Time to Clear Out of Your System
- 11. Days to Reach a Steady State
- 12. Shelf life
- 13. Comments
- 14. Depakote Ratings, Reviews, & Other Sites of Interest
- 15. References
Other Forms: Extended-release tablets, sprinkles
1. Other brand names & branded generic names1
- Depalept Chrono: (Israel)
- divalproex semisodium - international nonproprietary name hardly anyone uses
- Epival (Canada)
- Valcote (Colombia, Peru)
- And if not now, eventually the extended-release/chrono/retard version of every brand/branded generic version of sodium valproate on the planet that isn’t already an extended/prolonged-release form of sodium valproate.
- Epilepsy: Monotherapy (used by itself) and adjunctive treatment (i.e. you must use another drug along with it) for a variety of epileptic seizures. These include complex partial seizures and absence seizures. Depakote is approved for use with epilepsy for adults and children aged 10 and up.
- Acute Bipolar mania
- Treatment for types of Epilepsy not listed (e.g. primarily generalized tonic-clonic seizures)
- Borderline Personality Disorder (BPD)
- PTSD - surprisingly effective in treating depression associated with PTSD.
- Drug Dependencies:
- Cyclothymia, with or without PMS
- Sleep Disorders
- Sleep consolidation in PLMD. Not so much to stop your legs from moving, although it did that a little, but to help you sleep through all the kicking, which it did. I guess this one is recommended for people who sleep alone.
- Schizophrenia and Schizoaffective Disorder
- Alzheimer’s-related disorders
Proven to be effective for wide spectra of epilepsies and bipolar disorders. It’s been around for so long that the long-term effects are well known and well documented. If you can get past the initial side effects and get used to a valproate medication, you don’t have to worry about anything biting your ass in the long run. In that your doctor should know all the potentially serious bad shit that can happen, like liver failure, and how to prevent it, like making you get a liver function test between one and four times a year2.
The side effects suck donkey dong! The valproates are amongst the harshest meds to take. Everyone (read: the bipolar) hates them so much that they’ve given the entire class of AEDs/anticonvulsants a bad name.
The usual for antiepileptic drugs - strange dreams, wanting to sleep a lot, your memory will be a bit iffy and so forth. Plus a special set for valproates: instant old age. You’ll get fat, bald, tired, confused, dry & itchy skin, uninterested in sex, unable to hold your liquor, lose your teeth, and whatever you don’t puke will give you heartburn and/or the runs. Fortunately these side effects are both dosage-dependent (the more Depakote you take the more likely it is you’ll get them and/or the worse they’ll be) and most, like the nausea and other GI problems, are usually temporary. Also Depakote ER is easier on your stomach than immediate-release Depakote and valproic acid.
Unfortunately two side effects people complain about the most - weight gain and hair loss - tend to stick around, as does the occasional tremor and urge to yell at kids to get off of your lawn. At least you can take antacids like Maalox to deal with the GI problems. You can also take Depakote ER twice a day instead of once a day to further minimize nausea. You cannot take Pepto-Bismol and a valproate, as the active ingredient of Pepto-Bismol related to aspirin, and aspirin and valproates is a big no-no. Sometimes a really big no-no. The same goes for Alka-Seltzer.
Edema. Being more prone to respiratory infections. Getting a ringing in your ears.
Irreversible deafness (ouch!) and bone pain. I told you you’d get instantly old.
- Taking Depakote (divalproex sodium) with food helps reduce a lot of the gastrointestinal problems. In fact the sprinkles capsule is designed to be opened up and mixed in with stuff like “applesauce or pudding”. So if the extended release tablets don’t help with the GI issues, you might try literally mixing the sprinkles with food.
- Depakote (divalproex sodium) interacts with aspirin. Aspirin prevents you from metabolizing Depakote properly, so you’re better off with Aleve (naproxen sodium) or Tylenol (acetaminophen). Ibuprofen is OK, but only if you’re taking no more than 400mg a day. While there is no documented interaction, and , I’d be too freaking paranoid to take Tylenol and a valproate at the same time for more than a couple of days.
- Your doctor had better damn well be telling you about the regular blood work you need, to check your valproate levels and to make sure your liver is functioning normally.
- Depakote can sap your body of vitamin D, folic acid, and maybe even calcium. So ask your doctor about tests for vitamin D and calcium levels and supplements. You should probably take 400–1,000mcg of folic acid in any event, but no more than that, otherwise it might interfere with how well Depakote works. That folic acid may help you feel a lot less lethargic.
I Forgot Why I Cake Topamax
Depakote, like lithium, is all about blood levels. It’s also about which FDA-approved ailment we’re discussing. As always it’s adult dosages. While Depakote ER is supposed to be a once-a-day pill, taking Depakote ER twice a day works a lot better. That method reduces GI-related side effects like nausea, and a lot of people have reported it’s just more effective that way.
Depakote ER (which is pretty much all that gets prescribed these days)
The recommended initial dose is 25 mg/kg/day given once daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In a placebo-controlled clinical trial of acute mania or mixed type, patients were dosed to a clinical response with a trough plasma concentration between 85 and 125 mcg/mL. The maximum recommended dosage is 60 mg/kg/day. —Depakote ER PI sheet
Depakote Delayed Release (or: immediate release, as it is known in reality)
The recommended initial dose is 750 mg daily in divided doses. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg/mL. Maximum concentrations were generally achieved within 14 days. The maximum recommended dosage is 60 mg/kg/day. —Depakote PI sheet
What do they think we are crazy or something?
Then, get this, the maximum recommended dosage is 60mg/kg/day. What does that mean? It means if you weigh 150 pounds your doctor could keep upping your dosage to 4,000mg a day if you’re still flipping out! After just two weeks!
That, friends, is crazy. And why God invented antipsychotics. Zyprexa is the drug you want if you’re so high on your own brain that Charlie Sheen thinks you’ve gone too far and need to calm the hell down right now. Unless you can’t take antipsychotics. Which may be why someone else is reading this and you’ve been prescribed Depakote. In that case, shut the fuck up and take your meds, because if you really are that manic getting as much Depakote in you as soon as possible is going to suck a lot less than being batshit crazy longer than you need to be.
If you aren’t that crazy right now, either because you’re taking something else just from the point of a starting dosage, beginning with 500mg a day, or even lower, at three times a day (as the study with the ultra-rapid titration used) seems to be the way to start Depakote. From what I’ve read in the support groups the people whose doctors prescribe it that way bitch about the side effects a lot less. A least some doctors are reading the studies or these data are making it to conferences.
you start at 250mg taken twice a day (hey, it’s the minimum 500mg a day that seems to work). After that you can move up to 750mg a day then 1,000mg a day. Clinical trials don’t support dosages higher than that and I haven’t researched migraines.
The initial dosage is based on your weight. Why the hell not? Personally I think that’s better than just throwing 750mg a day at someone and ramping up drastically like they recommend for the bipolar.
While weight isn’t always a good factor at determining how burly your liver is, until tests of liver enzyme functions are more widely available, it’s as good a guess as any. So you start at 10 to 15mg/kg/day. So for that 150-pound person that’s between 650 and 1,000mg a day. Abbott is all about taking it two times a day. The only study I’ve found that suggests a three-times-a-day dosing schedule for epilepsy was comparing immediate release to extended release. I haven’t found anything regarding starting at a lower dosage for epilepsy in adults to deal with the side effects. I guess this is a case of what sucks less, seizures or side effects? Anyway, after that you can up the dosage by 5–10mg/kg/day until the seizures abate or you max out at 60mg/kg/day or you reach the sweet spot of blood levels between 50 & 100.
Turns out weight has nothing to do with your liver, at least not as far as valproates - or medications in general - are concerned. Details below in the section on how to stop taking it. I’m just going to puss out like I did with Stavzor/Depakene/valproic acid. Epilepsy is just too freaking complicated.
For everything else, it’s up to your doctor and whatever studies your doctor is following.
In theory you should start feeling results once you’re in the therapeutic range of your blood levels. So for epilepsy that’s generally in the neighborhood of 50–100, and for bipolar it’s a wider range of 40–150. Getting to that blood level is between you and your liver. Once there it’s up to your brain if it’s going to respond to a valproate or not. So unlike most anticonvulsants where you feel something in a matter of days, or there’s a definite dosage where we can write, “here is where you should notice effect or not,” it’s just not like that with the valproates.
Slowly. With most crazy meds we suggest that you reduce your dosage by however much you increased it, but with the rapid loading dose method that is often used for severe mania, that’s not always such a good idea.
As the only discontinuation instructions Abbott supplied are “be freaking careful” our suggestion to talk to your doctor about is to reduce your dosage by 250–500mg a day every five to seven days. Based on the half-life of 16 hours you could make that three days, but with the PK being so non-linear combined with it doing weird shit like the tissue binding not being affected by weight above a certain point3, five to seven days is just safer. 4
For more information, please see the page on how to safely stop taking these crazy meds.
Half-life: 9–16 hours. It’s out of your system in 2–3 days.
Half-life is the average time it takes for you to process half of the drug’s active ingredient. If a drug has a half-life of around 24 hours and you take a dose of 100mg, you’ll have roughly the equivalent a 50mg dose after one day, a 25mg dose after two days, and so on. The rule of thumb is: multiply the half-life by five and you get how long it is for the dose you took to be cleared from your bloodstream5, so there’s nothing swimming around to attach itself to your brain and start doing stuff. That’s called “plasma clearance.” Complete clearance is a complex equation based on a lot of factors which may or may not: be published in the PI sheet, include personal data like your weight, or even completely figured out by corporate and independent researchers. It usually winds up being 2–5 days after plasma clearance no matter what6, but can take weeks. Sometimes a drug will clear from your brain and other organs before it clears from your blood.
Depakote is non-linear. So that’s why it’s good for borderline personality disorder! Anyway, that means you can’t pin down a hard number on it. I haven’t found a good number for it in any study.
Steady state is the flipside of half-life. This is when you can expect to get over side effects caused by fluctuating amounts of a medication in your bloodstream. Often, but not always the same amount of time as the plasma clearance above.
Known as Depabloat for its weight-gain effect, the harsh side effects of all members of the valproate family have given a bad name to all anticonvulsants. The thing is most of the side effects common to valproates aren’t as bad with Depakote (divalproex sodium), especially the weight gain. While some of these side effects may be countered by slower titration and two- or even three-times-a-day dosing, Depakote (divalproex sodium) is not always an easy medication to take. Which is too bad, because it is quite effective when it comes to things like classic Bipolar 1, mixed states - better than lithium in that study, rapid cycling, and generally the broad spectrum of bipolar disorder. Although Depakote (divalproex sodium) usually sucks when it comes to bipolar depression. And if you’ve got rapid cycling combined with Bipolar 2, Lamictal (lamotrigine) is the drug for you. Bipolar users who’ve been through a few meds report that brand name Depakote ER typically causes less weight gain and gastrointestinal effects than lithium and certainly less weight gain than Zyprexa (olanzapine). Especially if a slow titration and two, or even three times a day dosing is used. The bad rap Depakote gets for a lot of side effects, especially weight gain most likely comes from people who were taking generic valproic acid and being told that it’s the generic for Depakote (divalproex sodium), when it wasn’t. Generic Depakote wasn’t available in the US until 2008.
If you’re on Medicaid, getting charity treatment or even with an HMO you might be told you’re getting Depakote (divalproex sodium), but look carefully at the prescription. The odds are it’s for valproic acid. That’s generic Depakene. By the time it gets to your brain it’s the same thing, but the road for generic valproic acid is much rockier than that of brand name Depakote, or even generic divalproex sodium, and you’ll probably experience far more side effects than you would with actual Depakote ER. Although according to this study the difference in side effects shouldn’t be enough to make you stop taking valproic acid if you were taking Depakote before. I have my doubts about it. Aside from being obviously biased towards generic meds, the people in the study kept taking Depakote for a much longer time, and people who were crazy enough to be hospitalized tend to complain about side effects less.
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It’s always a good idea to check for drug-drug interactions yourself. Just because most people in the crazy meds business know about really important interactions (e.g. MAOIs and a lot of stuff, warfarin and everything on the planet) doesn’t mean the person who prescribed your meds told you about them, or the pharmacist has all the meds you take at their fingertips like they’re supposed to. Or they have the time to do their jobs properly when not dealing with complete idiots or playing Angry Farmers on the Faecesbooks.
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Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (Essential Psychopharmacology Series) Third edition by Stephen M. Stahl © 2008 Published by Cambridge University Press
The Prescriber’s Guide (Essential Psychopharmacology Series) Third edition by Stephen Stahl © 2009 Published by Cambridge University Press.
Physicians’ Desk Reference Editions 53, 56, & 64 © 1999, 2002, & 2010
Instant Psychopharmacology 2nd Edition Ronald J. Diamond MD © 2002. Published by W.W. Norton
Essential Neuropharmacology: The Prescriber’s Guide Stephen D. Silberstein, Michael J. Marmura © 2010
Pharmacotherapy for Mood, Anxiety, and Cognitive Disorders Stuart A. Montgomery, Halbreich Uriel © 2000
Antiepileptic Drugs René H. Levy, Richard H. Mattson, Brian S. Meldrum, Emilio Perucca © 2003
The Complete Guide to Psychiatric Drugs Edward Drummond, MD © 2000. Published by John Wiley & Sons, Inc.
Partial Seizure Disorders Mitzi Waltz © 2001. Published by O’Reilly & Associates.
The Bipolar Disorder Survival Guide David J. Miklowitz, Ph.D © 2002. Published by The Guilford Press.1 The term "branded generic" has three meanings:
1) A generic drug produced by a generics manufacturer that is a wholly-owned subsidiary of the company that makes the branded version. E.g. Greenstone Pharmaceuticals makes gabapentin, and they are owned by Pfizer, who also own Parke-Davis, the makers of Neurontin.
2) A branded generic is also a generic drug given a 'brand' name by the manufacturer (e.g. Teva's Budeprion), but otherwise has the same active ingredient as the original branded version (Wellbutrin).
3) A branded generic is also a generic drug given a 'brand' name by the manufacturer (e.g. Sanofi-Aventis' Aplenzin, which is bupropion hydrobromide) and uses a salt of the active ingredient that is different from the original branded version and other generics (Wellbutrin, Budeprion and all the others are bupropion hydrochloride). We aren't sure if that really makes a difference or not. The FDA says they're the same thing. As usual, the data are contradictory, but most evidence indicates that the FDA is right and the differences are negligible.
For our purposes a "branded generic name" refers to the second and third definitions.
2 The vast majority of liver problems show up in the first 6 to 12 months of use, especially in the bipolar, as we usually get the most aggressive titration schedules (in English: the highest dosages the fastest) and our livers are often fucked-up to start with thanks to mania-inspired hepatitis, cirrhosis, and other problems. For most people an annual liver function test is more than enough. For anyone who takes a high dosage of a valproate, smokes, takes other medications (regardless of what they treat) that induce CYP or UGT enzymes, drinks alcohol, or eats a lot of charbroiled meat (I'm not joking), more than one liver function panel and an annual complete blood count would be a good idea.
3 In English…uh, well, you know how they like to base the dosage on how much you weigh, because it has to do with how well the drug sticks to your innards? No? Then I can't do much more than that. Sorry.
4 If you've been taking valproic acid, or any drug, for years and have been adjusting the dosages up and down - as is often the case with AEDs - a perfect mirror-image taper is obviously not going to work.
5 Based on Julien's calculations from A Primer of Drug Action, the half-life multiplied by five is the generally accepted estimate of how long it takes a single dose of any given drug to be eliminated from the blood stream/plasma of someone with a normal metabolism. That's also the rough estimate for steady stage if they can't get, or won't provide a number for that.
6 For crazy meds. I have no idea what the average complete clearance is for other types of medications. For all I know there are drugs that utterly vanish from your system in under five passes, and others that won't let go of your squishy bits for years after you stop taking them.
7 Thank you! I'll be here at least 72 hours. Be sure to tip your content provider. And don't try the veal, it's cruelicious!
If you have any questions not answered here, please see the Crazymeds Depakote discussion board. We welcome criticisms of the articles, notifications of bad links, site problems, consumer experiences with medications, etc. I’m not always able to write back. Hence I never answer questions about meds via e-mail that are answered by this or other articles. Especially if they have been repeatedly asked on the forum. That’s why we write these damn things. Questions about which meds are best for your condition should also be asked on the forum; because this is a free site, so the price of admission is making things easier for somebody else searching for the same answer. We don’t deal with children on the forum or in private because after doing this for ten years I don’t have the emotional stamina to deal with kids who have brain cooties. How to contact Crazymeds. — Jerod Poore, CME, Publisher Crazymeds (crazymeds.us)
|Last modified on Monday, 04 May, 2015 at 14:46:16 by JerodPoore||Page Author Jerod Poore||Date created|
|“Depakote (divalproex sodium ): a Review for the Educated Consumer.” by Jerod Poore is copyright © Jerod Poore||Published online 2011/04/25|
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Almost all of the material on this site is by Jerod Poore and is copyright © 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, and 2015 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and something along the lines of following disclaimer, I’m usually cool with it.
All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else. Plus we are big pottymouths and talk about S-E-X a lot.
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Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained from the medications’ product information / summary of product characteristic (PI/SPC) sheets and/or medication guides - which is all you get from sites like WebMD, RxList,
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1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.
2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.
3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?* I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion as anonymity on teh Intergoogles. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.
* Yes, I know I’m using open source browsers. I also test the site using the now-defunct IE and Safari browsers. Their popularity - and superiority - killed IE and Safari, so that’s why I rely on the open source browsers. It’s like brand vs. generic meds. Sometimes the generic is better than the brand.